NEJM publishes interim results from phase I trial of bb 2121 for multiple myeloma

Celgene Corporation and bluebird bio, Inc. announced that the New England Journal of Medicine (NEJM) has published interim results from CRB 401, the ongoing phase 1 study of bb 2121, the companies’ lead investigational BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy candidate for patients with relapsed and refractory multiple myeloma. The manuscript, “Anti-BCMA CAR T Cell Therapy bb2121 in Relapsed/Refractory Multiple Myeloma”, published in NEJM includes key safety and efficacy results from the dose escalation and first expansion cohort, including a minimum of six months follow up on all subjects.

As of the data cut-off date of April 30, 2018, manageable safety and deep and durable responses were reported in the first 33 patients infused with bb 2121 BCMA-targeted CAR T-cells. Patients in the study were heavily pre-treated, with a median of seven prior multiple myeloma treatment regimens (range, 3 to 23), which included prior treatment with immunomodulatory drugs, proteasome inhibitors and daratumumab in the majority of patients. All but one patient had previously received an autologous stem cell transplant. For the first 33 patients, the most common grade greater than 3 events were hematologic toxicities, including neutropenia (85%), leukopenia (58%), anemia (45%) and thrombocytopenia (45%). Neurotoxicity all-grades occurred in 14 (42%) patients; 13 (39%) were grade ?2 and one patient (3%) had grade 4 neurotoxicity which resolved within one month. Twenty-five (76%) patients experienced cytokine release syndrome; 23 (70%) were grade greater than 2 events and two (6%) were grade 3 events; all events were reversible. Infection occurred in 14 (42%) patients; two were grade 3 (6%) and there were no grade 4 events. Peak CAR T cell expansion was higher in patients with cytokine release syndrome and CAR T-cells remained detectable in the blood in 57% of patients at six months following infusion.

Treatment with bb 2121 resulted in an 85% objective response rate (ORR) with 45% of patients achieving a complete response (CR) (n=15) and an additional 27% of patients (n=9) achieving a very good partial response (VGPR) to yield a greater than VGPR rate of 73%. Sixteen responding patients were evaluable for assessment of minimal residual disease (MRD) and all tested MRD negative at one or more time points. Responses to bb 2121 CAR T-cell infusion occurred early, with a median time to first partial response or better of 1.0 month (range, 0.5 to 3.0), and responses were durable, with a median duration of response of 10.9 months (95% CI, 7.2 to not estimable). Researchers observed that greater CAR T-cell expansion occurred in responding patients. Responses were observed independent of tumor or serum BCMA levels. Median progression-free survival among all 33 patients was 11.8 months (95% CI, 6.2–17.8).

Potential approval of bb2121 in the U.S. is anticipated in the second half of 2020.